Member Info for Alquemie

Bless...Bothwell has his internet privileges back.

It's been pointed out before that reports of this type, historically compiled by minimum wage Indian graduates, now likely replaced by even cheaper AI, may be less than authoritative. Of the mentioned companies, all with the exception of Menarini (Priligy, now generic) and Absorption (Promescent- OTC delay spray) abandoned PE more than a decade ago (several no longer exist).

Perhaps reference to actual Fortacin sales (essentially static at around €1m gross since 2018) might give a more realistic indication of growth?

Bothwell, Recordati launch activities and prescriber-directed promotion were commensurate with market potential and limited clinical data. Rx was abandoned only after input from a specially convened urology expert panel. Lack of OTC promotion due to Blue Book type restrictions on efficacy claims, and was considered pointless in the absence of differentiation from other delay sprays, alongside the expectation of no more than token sales.

US has always been a total fantasy, pursuit only maintained to preserve an illusion of value. Ask yourself why, with such low technical barriers, no pharma company has submitted a PE NDA in over two decades.

A reasonable summation. To add a bit of colour:

China approval not impossible, but long odds due to the study material being different from the licenced product. PSNW (and the lifeboat company) both long liquidated which could confound access to historical CMC information. And why no pivotal data publication when the Pk/tox studies appeared tout suite?

Zezheng Biotechnology commencing Phase III, virtually identical to Fosun study with the important difference of Fortacin being the active comparator. Principal investigator and trial sites as used by Fosun. Domestic manufacture, no issues around ex-China supply. Generic in the market by 2027? Generic ("Lidonair" ) already aunched in India by Cipla, €5 for double the doses.

US hope died around 15 years ago: the abysmal Phase II and subsequent FDA knockbacks just hammered more nails in.

Dapoxetine never approved in Japan, no regulatory precedence for PE drugs. Pk/tox studies an absolute pre-requisite, not clear as to whether EMA endpoints might be acceptable. Submission, if ever, is years away, Market awash with domestic and imported delay sprays.

Net EU sales to wholesalers c. €1m after six years, demand completely met by two pallets worth a year. Royalty ceases in 3 years, divestment of the OTC business on the cards as CVC shape the company up for exit. Possible impact from Genetic sale and 2025 F-gas quota implementation.

DLI aging clock running very slowly, antiquated and not validated. The woo-woo wellness sector not interested, despite longevity focused consumer service companies claiming waiting lists of 100s of thousands of punters for subscriptions and bolt-on investigations.

Sounds as though the submission has survived initial screening, essentially an admin gatekeeping step to ensure that all sections are present and correctly formatted, before NMPA commits time and resource to technical and clinical assessment (and the problematic CMC history).

In passing, CVC finally has a buyer for Genetic SpA (NB Renaissance, a private equity firm). No takers for CVC's share of Recordati though, either from private equity nor an aborted reverse merger with an Italian pharma. Strategy now appears to be managed retreat, with equity sell-off in tranches (5% gone last month). Divestment of the OTC business and increased focus on high margin rare disease on the cards.

DLI's lack of value becomes clear when you consider their offerings in context. Serious aging clock research is focused on methylation or proteomic markers: DLI have opted for a panel of routinely measured biometrics, being cheap but with poor accuracy as biological age determinants, the notion being that a low-cost if next to useless approach will appeal to the woo-woo sector, which is always on the lookout for expensive bill-padding gimmicks.

This low-tech, easily emulated, non-validated approach means that they are frozen out of high value licensable pharmaceutical and healthcare applications and highly unlikely to satisfy the very savvy insurance industry which knows a thing or two when it comes to actuarial prediction.

It's telling that DLI shied away from entering the Biomarkers of Aging Consortium competition, where some 37 commercial and academic teams have submitted more than 550 clocks, to go mano a mano with regard to their precision in age and mortality prediction. Personal view is that In Silico leapt at the chance to deep six a dead-end high school project level approach for beer and pizza money, particularly as the company was already moving away from a longevity focus towards broader AI drug development acceleration.

You are not alone. No one, regardless of lifespan, will live long enough to see DLI create value.

And this "large shareholder", Bothwell- is he or she in the room with you now?

Or are the auditory hallucinations back again?

I'd worry less about time to review, than with what the NMPA will make of the dossier, specifically, the bioequivalence/toxicity and registration studies being conducted with material different in specification and manufacture from that proposed for commercial supply.

Even if eventually approved, there's no guarantee that Fosun, which has moved away from low value domestic products, will bother to launch something of such modest potential, and which is excluded from the NRDL and vulnerable to competition from cheaper Class 3 products.

USA "still on"?...Revenue from Deep Longevity?...Bless... Will you be leaving sherry and a mince pie out for Santa, Bothwell?

2024...Year of the Dragon...2025...Year of the Squeaky Bum...

Off the meds again, Bothwell?

Translated from a Chinese pharma newsfeed and not big on detail, but a second company, Lianhuan Pharmaceutical has received NMPA authorisation to commence clinical development of a Fortacin look-a-like, the other being Zezheng Biotech, which has already completed two biodistribution/tox studies.

Attraction is likely the low technical hurdle to approval (and not the very modest market), and may never reach submission but home-grown versions will have the advantage of domestic manufacture and significantly lower cost than ex-China supply limited by European F-gas phasedown. If Fosun ever submits for approval (increasingly unlikely for a host of reasons), RPG royalty will be cut off at the knees if a generic hits the market.

"Fiasco", eh? Very apt given its origin as a round-bottomed glass wine flask which could only stand up when wrapped in something. Woven blanched straw for Chianti bottles, and a weave of lies, disinformation and sheer fantasy in the case of RPG.

Mid-July...tick...tock...

Not in my nature to say "I told you so", but hey...I told you that this was dead last February when the Phase II data was made public. Caveat emptor, Mr Praline.

Now let's see...what else might they be gaslighting you poor old shareholders about? Shortcomings in the NMPA dossier? Perhaps something to do with the requirement to include measurement of the genotoxic metabolites 2,6-dimethylaniline and o-toluidine in the Pk/tox studies? As expected, no issues in male or female subjects, but bless me, manufacture and specification have changed since Oompa Loompa clinical supply and of course , there's no genotox data for the Made in Italy version.

Hmm...wonder if the NMPA will let this slide...? And 14 months on, still no release of the allegedly stellar Phase III data.

Tick...tock...

Allow me:

https://tinyurl.com/mrxth53z

The PLE Companies House filing sheds more light on the US regulatory situation. Not that it wasn't completely obvious from the Phase II data, but the FDA do not believe the PEBEQ to be fit for purpose and a second SPA request was denied last November. Strange not to have been mentioned back in March this year.

Cited verbatim below, although I've left out the waffle about "many positives in the FDA's response". True, nothing to stop the Phase III proceeding without a SPA or validated co-primary endpoint. Well, apart from no cash and zero chance of approval.

"On 2 June 2023, FDA replied to Plethora's request for SPA with a "no agreement" statement. The major observation is that the FDA is requesting on Estimand and SAP that was subsequently submitted to the FDA" ["estimand" relates to definition of treatment effect, SAP is the statistical analysis plan].

"On 6 November, the FDA replied again with a "no agreement" statement. The FDA is requesting that we generate evidence in respect of PEBEQ item 3 is "fit for purpose" and in the FDA's opinion this cannot be analysed until after our Phase 3 clinical trial is complete".

I sincerely hope that "Today's runs" is not a health report.

And yes, auditors consider RPG estimates of asset value to exceed what a purchaser might reasonably acquire the assets for, fair value being derived from future DCFs.

Curious as to why this has appeared long after the auditors signed off on the Annual Report- did they miss just how vigorously RPG have been jiggling the parrot, or is it only retrospective posterior protection? Still, you have to admire RPG's brass neck in trying to get away with a fantasy US milestone...cheeky...although they did get away with a fantasy IA valuation for the best part of a decade. Crystal clear that there's no expectation of a money fountain.

The reduction in the useful life of DLI intangible assets is puzzling, with the revised forecast assigning a useful life of just four years. This suggests that on acquisition, only licence(s) with In Silico were assigned to RPG, but no patent assignment (quick check indicates that IP remains assigned to In Silico, expiry many years away). I would have thought the licence term/useful life would have been at least 10 years from acquisition, not that it makes a difference in the scheme of things.

Going concern issue now looking more like a going...going...gone... concern issue.

My bad- that's the p value for global impression of severity, not bother. Latter given as a % recording a 1 point or greater improvement over baseline, and while twice as frequently recorded in the treatment group, still impossible to interpret in absence of objective treatment effect (moreover, may have involved only single treatment period encounter, and only 38 subjects on treatment. Even if there had been clear objective treatment difference, ITT population too small to support validation).

Bothwell, this certainly has the hallmarks of classic Gibson waffle, simply re-hashing past half-truths, and with lines lifted verbatim from past releases. Or has someone been helping you play with ChatGPT?

As for the PRO results "speaking for themselves", the published data screams "no significant difference in post-treatment IELT between treatment and placebo", a 50% placebo response versus 70% treatment response for subjective endpoints, and probably most damning of all with respect to PRO validation, no difference in global impression of change between treatment and placebo groups at end of treatment. True, the difference between means for Item 3 did reach significance (P = 0.0031), but impossible to interpret this in the absence of clear-cut objective and subjective treatment effects.

So, do you have the guts to look at the data (simple comparison of means is all that's needed), or too frightened to test faith with fact? Or why not cut through the waffle and ask outright "has the FDA accepted that the Phase II study data validates bother as an acceptable co-primary endpoint, and that the PEBEQ is now validated as an appropriate instrument"?

Dearie me, Bothwell, you really don't get it...or has your friend been whispering?

Genetic was approved on the back of a Type II variation for Fortacin manufacture, with revised specs and accelerated stability data. The bioequivalence and Phase III studies used clinical trial supply from PSNW, different in several respects to the current commercially supplied version. Reference product is Senstend for which no CMC data exists (and for which MHRA authorisation may have expired). NMPA may not accept the Fortacin variation/dossier equivalence without supporting data and may require RT stability (zone 1-IVa inclusive).

On supply, Genetic operate two pMDI lines for three generic products. Fortacin requirement is so low that I believe it's being manufactured on a separate small volume line used for product work up and clinical trial supply, not the commercial lines. The HFA phasedown means that no contract pMDI manufacture in Europe will increase capacity until low-GWP propellants are approved and available (China also accepts the Kigali amendment, albeit with different timetabling).

As to claims around study data, the "strongly positive" Phase II failed to demonstrate any significant post-treatment difference between Fortacin and placebo (the latter giving a mean six-fold increase in IELT over baseline, p=0005, versus an eight-fold increase for Fortacin). No difference in perception of post-treatment benefit between drug and placebo (p=0.3585!). Study data is in the public domain, and explains why no progress has been made in the nearly 30 months since first FDA review. Now, China Phase III did involve a longer treatment period, so perhaps less chance of drug/placebo overlap, although a year on, only RPG have referenced the study, whereas Fosun was very quick to publish the bioequivalence data (publication of Phase III data would not impact on NMPA review). I wonder what Fosun makes of the US data?

Six years to make up the shortfall, Bothwell...tick....tock.

Bothwell, you appear to have perked up since your whiney "I've lost all my money" posts. Tell me, has your "friend" manifested himself again or are you back on the lithium?

Do keep up, Bothwell. Dr "Bigger than Viagra" not involved since end 2022, currently playing around with some ancient injectable ED treatment (3 parts sand, 1 part cement?).

Dougie's six years a tad overoptimistic- US died forever five minutes after first Phase II data analysis, China submission likely permanently hamstrung through missing CMC data (and perhaps dodgy results), along with macro issues (supply, Fosun restructuring, market potential and the looming HFA phasedown). Hope you have a pension Plan B in place.